CN104127874B - GPR120 agonist TUG891 prevents and treats osteoporotic application - Google Patents
GPR120 agonist TUG891 prevents and treats osteoporotic application Download PDFInfo
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Abstract
The invention discloses GPR120 agonist TUG891 and prevent and treat osteoporotic application, mesenchymal stem cells MSCs is had by high concentration TUG891 significantly facilitates bone differentiation, and the proliferation activity of mesenchymal stem cells MSCs can be obviously improved, and low concentration group can not promote Osteoblast Differentiation and the multiplication capacity of cell, even can partial down-regulation Osteoblast Differentiation and proliferation potential.In castration mouse bone rapping type, TUG891 can improve distal femur Grafting Cancellous Bone Bolt micro structure, increase the mineral deposition rate of distal femur, show that TUG891 can improve bone micro-structure by promoting the proliferation and differentiation of mesenchymal stem cells MSCs, play and prevent and treat osteoporotic effect.
Description
Technical field
The invention belongs to osteoporotic Prevention Technique field, relate to GPR120 agonist TUG891 and prevent
Control osteoporotic application.
Background technology
Osteoporosis (osteoporosis, OP) is degeneration, general, metabolic bone disease,
It is that osseous tissue bone loss, structural change and the biomechanical property caused by Different types of etiopathogenises goes down, easily
Fracture, the physical and mental health of serious threat old people.
Along with the progress faster of aged tendency of population, the ratio of China's senile osteoporosis increases year by year.?
In osteoporotic generation development process, in marrow, fat dramatically increases, and has the red of hematopoietic potential during birth
Bone marrow is gradually substituted by yellow bone marrow, and accounting for the major part in yellow bone marrow volume is yellow or brown fat group
Knit, and be almost full with medullary cavity.But, in marrow, function and the origin of fatty tissue there is no final conclusion,
One of which saying be mesenchymal stem cells MSCs with advancing age or the stimulation of osteoporosis microenvironment
Lower Osteoblast Differentiation reduced capability, becomes fat differentiation capability to strengthen.And fatty tissue can be with shape by lipolysis
Becoming fatty acid, numerous fatty acid of classifying has been found to contact closely with bone metabolism.But its Bone Defect Repari,
The effect participated in knitting and the physiological mechanism related to are extremely complex, and the most still without final conclusion.
TUG891 in the last few years as treatment diabetes and improve the primary drugs of insulin resistant,
Endocrine field has become study hotspot.GPR120 is as middle long-chain unsaturated fatty acid receptor, and it swashs
Dynamic agent TUG891 effect in bone metabolism, the bone formation under the conditions of such as osteoporosis and knitting,
And the regulating and controlling effect in Proliferation of Bone Mesenchymal Stem Cells atomization, have no report at present.
Summary of the invention
It is an object of the invention to provide GPR120 agonist TUG891 and prevent and treat osteoporotic application,
TUG891 can be applicable to prevent and treat the preparation of osteoporotic medicine.
For reaching above-mentioned purpose, present invention employs techniques below scheme:
GPR120 agonist TUG891 is used for preventing and treating the application in osteoporotic medicine in preparation.
GPR120 agonist TUG891 is used for promoting the medicine of Proliferation of Bone Mesenchymal Stem Cells in preparation
In application.
The medicine that GPR120 agonist TUG891 suppresses for anti-mesenchymal stem cells differentiation in preparation
Application in thing.
GPR120 agonist TUG891 is used for improving ALP activity in mesenchymal stem cells MSCs in preparation
Medicine in application.
GPR120 agonist TUG891 is used for improving in mesenchymal stem cells MSCs in preparation and facilitates bone to divide
Change the application in the medicine of Gene A LP, OCN and Runx2 expression.
The dosage of GPR120 agonist TUG891 is at least 10 μ g/kg.
The dosage of GPR120 agonist TUG891 is 30-50 μ g/kg.
The present invention has a following useful technique effect:
TUG891 is free of toxic effects to Marrow Mesenchymal Stem Cells (mBMSC), remarkably promotes
MBMSC multiplication capacity；And the osteogenic ability of mBMSC can be improved, increase the work of cell ALP
Property, increase the expression of Bone formation-related gene.In castration mouse model, TUG891 can improve femur
Distal bone micro structure, increases the mineral deposition rate of distal femur.
Mesenchymal stem cells MSCs is research Oesteoblast growth, the more common cell model of differentiation, mirror
In the TUG891 effect to BMSC, stem cell is had and significantly promotees ossification by it, promotes propagation,
And by activating Ras-Raf-MEK-Erk1/2 approach, it is obviously improved BMSC to Osteoblast Differentiation, finally
Play the osteoporotic effect of preventing and treating.Ovariectomized mice model is conventional post menopausal bone rapping type, logical
Cross continuous femur stage casing Intramedullary injection give with various dose TUG891, hence it is evident that to Grafting Cancellous Bone Bolt micro structure
Protected effect, and improve mineralising deposition, show that it can play prevention and treatment post menopausal bone pine
Effect.
Therefore, TUG891 can be applicable to osteoporotic preventing and treating, especially at preventing and treating medicine for treating osteoporosis
Preparation in apply.
Accompanying drawing explanation
Fig. 1-1 is the variable concentrations TUG891 effect to Cellular alkaline phosphatase (ALP) activity.
Fig. 1-2 is the variable concentrations TUG891 effect to cellular matrix calcium deposition.
Fig. 1-3 is the variable concentrations TUG891 impact on cell Osteoblast Differentiation gene expression dose.
Fig. 2-1 is the impact of variable concentrations TUG891 cell proliferation effect, Merge be Brdu with
The merging of DAPI coloration result.
Fig. 2-2 is the variable concentrations TUG891 effect to cell MTT activity.
The mBMSC that Fig. 3-1 knocks out for the GPR120 work to Cellular alkaline phosphatase (ALP) activity
With.
The mBMSC that Fig. 3-2 knocks out for the GPR120 effect to cellular matrix calcium deposition.
The mBMSC that Fig. 3-3 knocks out for the GPR120 impact on cell Osteoblast Differentiation gene expression dose.
Fig. 4-1 improves the Micro-CT of OVX mouse femur far-end Grafting Cancellous Bone Bolt micro structure for TUG891
As a result, wherein, a:sham；b:OVX；c:OVX+0.1μg/kg TUG891；d:OVX+1μg/kg
TUG891；e:OVX+10μg/kg TUG891；f:OVX+30μg/kg TUG891；g:OVX+50μg/kg
TUG891；h:OVX+100μg/kg TUG891；A represents femur cross section；B represents femur longitudinal section.
Fig. 4-2 improves the VG dyeing knot of OVX mouse femur far-end Grafting Cancellous Bone Bolt micro structure for TUG891
Really, wherein, a:sham；b:OVX；c:OVX+0.1μg/kg TUG891；d:OVX+1μg/kg TUG891；
e:OVX+10μg/kg TUG891；f:OVX+30μg/kg TUG891；g:OVX+50μg/kg TUG891；
h:OVX+100μg/kg TUG891。
Fig. 5-1 is that internal various dose group TUG891 processes the detection osteogenesis of descending Collateral
As a result, wherein, a:sham；b:OVX；c:OVX+0.1μg/kg TUG891；d:OVX+1μg/kg
TUG891；e:OVX+10μg/kg TUG891；f:OVX+30μg/kg TUG891；g:OVX+50μg/kg
TUG891；h:OVX+100μg/kg TUG891.
Fig. 5-2 is the mineral apposition rate of the mouse femur far-end obtained according to Fig. 5-1, wherein, a:sham；
b:OVX；c:OVX+0.1μg/kg TUG891；d:OVX+1μg/kg TUG891；e:OVX+10μg/kg
TUG891；f:OVX+30μg/kg TUG891；g:OVX+50μg/kg TUG891；
h:OVX+100μg/kg TUG891。
Detailed description of the invention
With embodiment, the present invention is elaborated below in conjunction with the accompanying drawings, described in be explanation of the invention and
It not to limit.
MBMSC is Marrow Mesenchymal Stem Cells, can break up to osteoblast, is research
Oesteoblast growth, the more common cell model of differentiation, under physiological condition, mBMSC is to promote in vivo
Enter one of osteoblast generation important channel with growth and osteogenesis.And mesenchymal stem cells MSCs
Proliferation potential also play an important role during bone metabolism and bone remoulding.FAA swashs
Dynamic agent is the more common external medicine for activating GPR receptor family, for observing TUG891 to one-tenth
Bone differentiation and the impact of cell proliferation, so selecting mice BMSC as cell model.Ovary excises
(castration) mouse model, as animal model, is bone rapping type after conventional simulation postmenopausal women.
The most external TUG891 stimulates the concentration screening of Osteoblast Differentiation to Marrow Mesenchymal Stem Cells
1.1, mBMSC is laid on 6 orifice plates, after being paved with, adds the dexamethasone Han 0.1uM, 10mM
The a-MEM culture medium of sodium glycerophosphate and 50ug/mL ascorbic acid carries out osteogenic induction cultivation.?
In osteogenic induction incubation, give 0.1,0.5,1,5,10,30,50,100 μMs of TUG891 simultaneously
Process.Osteogenic induction is carried out according to alkali phosphatase quantification kit (Shanghai outstanding person is beautiful) after cultivating 14 days
ALP is quantitative, collects cell, extracts albumen after cracking.Measure protein concentration, then according to test kit
Illustrate, carry out ALP detection by quantitative.
As Figure 1-1, abscissa is drug level to result, and vertical coordinate is ALP activity, with each group
The percent that absorbance OD value compares with the OD value of blank group (Con) is stated.Empty
White matched group is cultivated for giving merely osteogenic induction.Low concentration group (0.1,0.5,1 μM) TUG891 makees
With rear, cell ALP activity expression is remarkably decreased compared with blank group, high concentration group (30,50,
100 μMs) after effect, ALP activity expression raises, and in concentration dependent.ALP is that osteoblast divides
Change the crucial expressing protein in mid-term, for detecting the specific index of osteoblast differentiation, Osteoblast Differentiation ability
Reduction can be shown as ALP activity and reduce, and is inhibitory action to Osteoblast Differentiation, but through high concentration TUG891
After effect, ALP expresses increase, significantly enhances cell Osteoblast Differentiation ability.
1.2 calcium scoring dyeing: be laid on by mBMSC on 6 orifice plates, after being paved with, add containing 0.1uM
Dexamethasone, the a-MEM culture medium of 10mM sodium glycerophosphate and 50ug/mL ascorbic acid is carried out
Osteogenic induction is cultivated.In osteogenic induction incubation, give 0.1 simultaneously, 0.5,1,5,10,30,
50,100 μMs of TUG891 process.Osteogenic induction rinses cultivation cell with PBS after cultivating 14 days, many
After polyformaldehyde is fixing, 1% Alizarin red staining 30 minutes, rinses 5 times with water, observes under inverted microscope
Calcium tuberosity deposits.
Result as shown in Figure 1-2, after low concentration TUG891 (0.1,0.5,1 μM) effect, tie by calcification
Joint is formed less, but after high concentration TUG891 (30,50,100 μMs) acts on, knuckle area
There is increase.Calcium nodiform becomes the mineralization stage of Osteoblast Differentiation, and high concentration group TUG891 process can show
Writing raising mineralising and form level, prompting TUG891 also can participate in osteogenesis in the Osteogenesis later stage.
The RT-PCR detection of 1.3 osteogenesis genes: be laid on by mBMSC on 6 orifice plates, after being paved with, adds
Containing 0.1uM dexamethasone, the a-MEM training of 10mM sodium glycerophosphate and 50ug/mL ascorbic acid
Foster base carries out osteogenic induction cultivation.In osteogenic induction incubation, give 0.1 simultaneously, 0.5,1,5,
10,30,50,100 μMs of TUG891 process.Osteogenic induction uses Trizol cell lysis after cultivating 14 days,
Extract intracellular mRNA, according to the program of real-time quantitative RT-PCR, to genes of interest ALP, OCN
And RUNX2 carries out detection by quantitative.
As Figure 1-3, as seen from the figure, low concentration TUG891 (0.1,0.5,1 μM) acts on result
After, cell Osteoblast Differentiation Gene A LP, OCN and RUNX2 expression relatively blank group (Con)
Declining, blank group is cultivated for giving merely osteogenic induction, high concentration TUG891 (30,50,100 μMs)
After effect, relatively blank group (Con) can remarkably promote osteogenesis gene and express.ALP, OCN and
RUNX2 gene is respectively the key gene in osteoblast differentiation mid-term and later stage, decides dividing of cell
Change level.The expression of low concentration TUG891 suppression Osteoblast Differentiation gene, and the effect of high concentration TUG891
After, Osteoblast Differentiation gene expression has rise, illustrates that high concentration TUG891 can be obviously improved between bone marrow and fills
Matter stem cell Osteoblast Differentiation ability.
The most external TUG891 concentration screening to Marrow Mesenchymal Stem Cells multiplication capacity
2.1 by mBMSC with 1 × 104/cm2It is inoculated in copolymerization Jiao's culture dish, treats that cell reaches 80%
After fusion, discard media alone (a-MEM culture medium), add containing 0.1,0.5,1,5,10,30,
50, the a-MEM culture medium of 100 μMs of TUG891 is in copolymerization Jiao's culture dish, after effect 48h, gives
After giving often group cell 5 μ g/mL Brdu pretreatment 2 hours, carry out Brdu immunofluorescence dyeing, DAPI
Nucleus is redyed.
Result is as shown in Fig. 2-1, and low concentration TUG891 (0.1,0.5,1 μM) is compared with blank
Can partly suppress mBMSC multiplication capacity, and high concentration TUG891 (30,50,100 μMs) is with empty
The proliferation potential that can be obviously improved mBMSC, cell quantity showed increased are compared in white comparison, and blank is right
TUG891 (0 μM) is not added according to for media alone.
2.2 by mBMSC cell with 2 × 103/cm2It is inoculated on 96 orifice plates, after cell covers with, abandons
Fall media alone, add the a-MEM containing 0.1,0.5,1,5,10,30,50,100 μMs of TUG891
Culture medium, in orifice plate, acts on 6h, 12h, 24h, 48h, the often multiple holes of group 6 respectively.To point of observation,
Utilize MTT colorimetry to screen suitable TUG891 activity and time, add the 5mg/mL of 20 μ L
MTT solution, after hatching 4 hours, add DMSO, shake 5 minutes, 492nm in microplate reader
Wavelength readings.
Result is as shown in Fig. 2-2, and abscissa is the TUG891 action time of variable concentrations, and vertical coordinate is
Cytoactive, with the absorbance OD value of each group, with blank group, (blank is media alone training
Support and do not add TUG891) the percent that compares of OD value state.As seen from the figure, same to Fig. 2-1
As a result, with concentration and the prolongation of action time of TUG891, mBMSC activity is gradually increased.Low
Concentration TUG891 (0.1,0.5,1 μM) can partly suppress mBMSC survival ability, and high concentration
TUG891 (30,50,100 μMs) can be obviously improved the proliferation potential of mBMSC, cell survival
Quantity showed increased.
3. detect its impact on Osteoblast Differentiation ability by knocking out GPR120
MBMSC is laid on 6 orifice plates by 3.1, after being paved with, adds the dexamethasone Han 0.1uM, 10mM
The a-MEM culture medium of sodium glycerophosphate and 50ug/mL ascorbic acid carries out osteogenic induction cultivation.?
In osteogenic induction incubation, give 50 μMs of TUG891 process simultaneously.After osteogenic induction is cultivated 14 days
Carry out ALP quantitatively according to alkali phosphatase quantification kit (Shanghai outstanding person is beautiful), collect cell, after cracking,
Extract albumen.Measure protein concentration, then according to the explanation of test kit, carry out ALP detection by quantitative.
As shown in figure 3-1, abscissa is cell class and drug level to result, and Con represents normal
MBMSC, KD are the mBMSC that GPR120 knocks out.Vertical coordinate is ALP activity, with the suction of each group
The percent that luminosity OD value compares with the OD value of blank group (Con) is stated.GPR120
The mBMSC cell ALP activity expression knocked out is remarkably decreased compared with blank group, and normal
MBMSC is after 50 μMs of TUG891 effects (Con+TUG 50 μMs), and ALP activity expression raises,
And the mBMSC that GPR120 knocks out (KD+TUG 50 μMs) after giving TUG891, ALP are active
Do not increase.ALP is the crucial expressing protein in osteoblast differentiation mid-term, for detection osteoblast differentiation
Specific index, Osteoblast Differentiation ability reduce can be shown as ALP activity reduce, to Osteoblast Differentiation for pressing down
Making use, GPR120 knocks out the ALP activity of cell and is decreased obviously, and illustrates that GPR120 is to Osteoblast Differentiation
Play indispensable effect.
3.2 calcium scoring dyeing: be laid on by mBMSC on 6 orifice plates, after being paved with, add containing 0.1uM
Dexamethasone, the a-MEM culture medium of 10mM sodium glycerophosphate and 50ug/mL ascorbic acid is carried out
Osteogenic induction is cultivated.In osteogenic induction incubation, give 50 μMs of TUG891 process simultaneously.Become
Self-bone grafting rinses cultivation cell, after paraformaldehyde is fixing, 1% Alizarin red staining with PBS after cultivating 14 days
30 minutes, rinse 5 times with water, under inverted microscope, observe calcium tuberosity deposition.
As shown in figure 3-2, mBMSC (KD) calcium scoring that GPR120 knocks out is formed less result,
And after high concentration TUG891 (50 μMs) processes (KD+TUG 50 μMs), knuckle area is without increasing.
Calcium nodiform becomes the mineralization stage of Osteoblast Differentiation, and GPR120 knocks out the mineralising of cell, and to form level notable
Declining, prompting GPR120 plays a significant role in the regulation and control of Osteogenesis later stage osteogenesis.
The RT-PCR detection of 3.3 osteogenesis genes: be laid on by mBMSC on 6 orifice plates, after being paved with, adds
Containing 0.1uM dexamethasone, the a-MEM training of 10mM sodium glycerophosphate and 50ug/mL ascorbic acid
Foster base carries out osteogenic induction cultivation.In osteogenic induction incubation, give 50 μMs of TUG891 simultaneously
Process.Osteogenic induction uses Trizol cell lysis after cultivating 14 days, extracts intracellular mRNA, root
According to the program of real-time quantitative RT-PCR, genes of interest ALP, OCN and RUNX2 are quantitatively examined
Survey.
Result is as shown in Fig. 3-3, as seen from the figure, after GPR120 knocks out, cell Osteoblast Differentiation Gene A LP,
OCN and RUNX2 expression declines, and gives the mBMSC high concentration that GPR120 knocks out
After TUG891 effect, osteogenesis gene is expressed without substantially rising.ALP, OCN and RUNX2 gene divides
Not Wei osteoblast differentiation mid-term and the key gene in later stage, decide the level of differentiation of cell.GPR120
Knock out the expression that can suppress Osteoblast Differentiation gene, illustrate that the rise of GPR120 can be obviously improved between bone marrow
Mesenchymal stem cells Osteoblast Differentiation ability.
4.TUG891 to effect osteoplastic in Mice Body
The foundation of animal bone rapping type: 40 8 weeks big BALB/c female mices, body weight is 20.84 ±
1.21g.The original body mass no difference of science of statistics of this experiment small mouse.Before excision ovary, first by them
Be placed under laboratory condition 1 week (i.e. ventilate in the isoperibol of good 20 DEG C, illumination in every 12 hours with
Alternately, water grain is enough, freely takes for dark).After adapting to 1 week, with pentobarbital sodium (50 mg/kg bodies
Weight) anaesthetize, the cut ovary of mice (castration, n=35) or sham-operation (n=5).Ovary excision is
By dorsal part approach for resection bilateral ovaries.Sham-operation means that bilateral ovaries is found in operation, but does not excises,
Directly sew up and close otch.
It is administered: mice is randomized, often group 5: Sham-operated control group (sham)；Simple ovary
Excision group (OVX)；(after ovary excision, every day is by femur stage casing for various dose TUG891 administration group
Intramedullary injection gives the TUG891 solution of 0.1,1,10,30,50,100 μ g/kg body weight respectively,
I.e. OVX+0.1 μ g/kg TUG891；OVX+1μg/kg TUG891；OVX+10μg/kg TUG891；
OVX+30μg/kg TUG891；OVX+50μg/kg TUG891；OVX+100μg/kg TUG891).
TUG891 solution: TUG891 is dissolved in DMSO and is diluted by deionized water.By femur stage casing marrow
Intracavitary administration is to not processing group (Sham-operated control group and simple ovary excision group) injected in mice same volume
Deionized water.Post operation starts to be administered for 1 week, successive administration 10 time-of-week.After administration completes, under anesthesia
Extract the left femur of every mice, remove the muscular tissue of adhesion, properly fix.
4.1 Micro-CT scanning detection bone micro-structures: the bone micro-structure of distal femur faces in advance by exploring track SP
Bed specimen Micro-CT scanning detects.Resolution is 8mm, and tube voltage is 50kV, and tube current is 0.1mA.
Process software by a desktop Micro-CT scanning to carry out rebuilding and 3D quantitative analysis.The scan ring of all specimen
Border is identical with the method for analysis.Femur scanning area is defined to distal stem dirt end, and primary pine proximally
Matter proximal end region extends 2.0mm.After eliminating skull and tail endplate regions, the cancellous bone region of vertebral body
It is comprised in each Micro-CT scanning constituency.In the region that these are to be scanned, spongy bone and cortical bone
Be demarcated as inner cortex surface of bone.The 3D parameter of selected region of interest is used for data analysis, including: bone
Mineral density, Connection Density, structure model index, bone trabecula quantity, bone trabecula thickness, bone trabecula
Separating degree and relative bone volume mark.The operator being scanned analyzing is blind to the processing procedure list of specimen.
Result is as shown in Fig. 4-1, and relative to Sham-operated control group, ovary excision result in mice spongy bone
The infringement of bone micro-structure, shows as bone mineral density, Connection Density, bone trabecula quantity, bone trabecula thickness
The decline of degree and relatively bone volume mark.Meanwhile, after ovary excision, structure model index separates with bone trabecula
Degree significantly improves.Result has significant difference.But, high dose (30,50,100 μ g/kg) TUG891
Administration group has substantially reversed the variation tendency of the bone micro-structure parameter that ovary excision causes, and plays holding femur
The effect of distal bone girder bone amount.Therefore, TUG891 can to postmenopausal osteoporosis play prevention and
Therapeutical effect.
4.2 carry out histology by VG dyeing: after the left femur of mice has been drawn materials, with 4%
Paraformaldehyde fixes 48 hours.All specimen 80% dehydration of alcohol, and use polymethyl methacrylate
(PMMA) embed.The Coronal thin slice that 240mm sheet is thick is cut, then with rotary microtome
All sections are polished into 20mm sheet thick, are used for carrying out VG dyeing.
Result as shown in the Fig. 4-2, relative to Sham-operated control group, simple ovary excision group bone trabecula quantity
Being decreased obviously, the distance between girder substantially broadens.After giving the process of high and low dose TUG891, high agent
Amount group bone trabecula infringement effect is substantially improved, and shows as increase and the bone trabecula spacing of bone trabecula quantity
Reduction.
5. Collateral detection osteogenesis and bone mineral deposition
The foundation of animal bone rapping type and administration are with 4.
Before sacrifice the 12nd day and the 2nd day intramuscular injection tetracycline (20mg/kg) respectively and calcium are yellow
Verdazulene (5mg/kg) carries out fluorescein labelling.Left femur is taken after putting to death mice, be fixed successively,
It is dehydrated, embeds and cut into slices (10 μm).Under the conditions of amplifying 200 times, measure tetracycline graticule yellow with calcium
Distance between verdazulene graticule.After obtaining average distance, then divided by natural law, i.e. can determine that mineral apposition rate.
Result is as shown in Fig. 5-1,5-2, and in all groups, area of new bone is labeled has gone up tetracycline and calcium is yellowish green
Element fluorescence.Relative to Sham-operated control group, the mineral apposition rate of simple ovary excision group is decreased obviously.
But, after high and low dose TUG891 processes, high dose group (30,50,100 μ g/kg) mineral
Deposition substantially increases, and this result is identical with external trend.To sum up, TUG891 can be by raising ore deposit
Electrodeposition substance rate and play protection Grafting Cancellous Bone Bolt micro structure effect.
In a word, mBMSC is had by high concentration TUG891 significantly facilitates bone differentiation, and can show
Write the proliferation activity promoting mBMSC, and low concentration TUG891 can divide by partial down-regulation mBMSC skeletonization
Change and proliferation potential.In castration mouse bone rapping type, TUG891 can improve distal femur spongiosa
Bone bone micro-structure, increases the mineral deposition rate of distal femur, shows that TUG891 can be by promoting bone marrow
The proliferation and differentiation of mescenchymal stem cell thus improve bone micro-structure, play and prevent and treat osteoporotic effect.Cause
This, FAA GPR120 specific agonist TUG891 can be applicable to osteoporotic preventing and treating,
Especially apply in the preparation of preventing and treating medicine for treating osteoporosis.
Claims (7)
1.GPR120 agonist TUG891 is used for preventing and treating the application in osteoporotic medicine in preparation.
2.GPR120 agonist TUG891 is used for promoting the medicine of Proliferation of Bone Mesenchymal Stem Cells in preparation
Application in thing.
3.GPR120 agonist TUG891 suppresses for anti-mesenchymal stem cells differentiation in preparation
Application in medicine.
The most according to claim 3, GPR120 agonist TUG891 fills between anti-bone marrow in preparation
Application in the medicine of matter stem cell differentiation suppression, it is characterised in that: GPR120 agonist TUG891
In preparation for the application improved in mesenchymal stem cells MSCs in the medicine of ALP activity.
The most according to claim 3, GPR120 agonist TUG891 fills between anti-bone marrow in preparation
Application in the medicine of matter stem cell differentiation suppression, it is characterised in that: GPR120 agonist TUG891
It is used for improving in mesenchymal stem cells MSCs in preparation and facilitates bone differentiation gene ALP, OCN and Runx2
Application in the medicine of expression.
6. the application as described in any one in claim 1-5, it is characterised in that: GPR120 is exciting
The dosage of agent TUG891 is at least 10 μ g/kg.
7. the application as described in any one in claim 1-5, it is characterised in that: GPR120 is exciting
The dosage of agent TUG891 is 30-50 μ g/kg.
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Non-Patent Citations (3)
| Title |
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| Exposure to omega-3 fatty acids at early age accelerate bone growth and improve bone quality;Netta Korena等;《Journal of Nutritional Biochemistry》;20140630;第25卷(第6期);623-633 * |
| GRP120的结构特征、生物学功能及作用机制;赵乃倩等;《生理科学进展》;20131231;第44卷(第4期);291-296 * |
| The Pharmacology of TUG-891, a Potent and Selective Agonist of the Free Fatty Acid Receptor 4(FFA4/GPR120)，Demonstrates Both Potential Opportunity and Possible Challenges to Therapectic Agonism;Brain D等;《MOLECULAR PHARMACOLOGY》;20131130;第84卷;710-725 * |
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